RESUMEN
Introduction: Percutaneous kidney biopsy (KB) is crucial to the diagnosis and management of several renal pathologies. National data on native KB in pediatric patients are scarce. We aimed to review the demographic and clinical characteristics and histopathological patterns in children who underwent native percutaneous KB over 24 years. Methods: Retrospective observational study of patients undergoing native percutaneous KB in a pediatric nephrology unit between 1998 and 2021, comparing 3 periods: period 1 (1998-2005), period 2 (2006-2013), and period 3 (2014-2021). Results: We found that 228 KB were performed, 78 (34.2%) in period 1, 91 (39.9%) in period 2, and 59 (25.9%) in period 3. The median age at KB was 11 (7-14) years. The main indications for KB were nephrotic syndrome (NS) (42.9%), hematuria and/or non-nephrotic proteinuria (35.5%), and acute kidney injury (13.2%). Primary glomerulopathies were more frequent (67.1%), particularly minimal change disease (MCD) (25.4%), IgA nephropathy (12.7%), and mesangioproliferative glomerulonephritis (GN) (8.8%). Of the secondary glomerulopathies, lupus nephritis (LN) was the most prevalent (11.8%). In group 1, hematuria and/or non-nephrotic proteinuria were the main reasons for KB, as opposed to NS in groups 2 and 3 (p < 0.01). LN showed an increasing trend (period 1-3: 2.6%-5.3%) and focal segmental glomerular sclerosis (FSGS) showed a slight decreasing trend (period 1-3: 3.1%-1.8%), without statistical significance. Conclusions: The main indication for KB was NS, which increased over time, justifying the finding of MCD as main histological diagnosis. LN showed an increase in incidence over time, while FSGS cases did not increase.
RESUMO Introdução: A biópsia renal (BR) percutânea é fundamental para diagnóstico e manejo de diversas patologias renais. Dados nacionais sobre BR nativa em pacientes pediátricos são escassos. Nosso objetivo foi revisar características demográficas, clínicas e padrões histopatológicos em crianças submetidas a BR percutânea nativa ao longo de 24 anos. Métodos: Estudo observacional retrospectivo de pacientes submetidos a BR percutâneas nativas em unidade de nefrologia pediátrica entre 1998 e 2021, comparando três períodos: período 1 (1998-2005), período 2 (2006-2013), período 3 (2014-2021). Resultados: Constatamos que foram realizadas 228 BR, 78 (34,2%) no período 1, 91 (39,9%) no período 2, 59 (25,9%) no período 3. A idade mediana na BR foi 11 (7-14) anos. As principais indicações para BR foram síndrome nefrótica (SN) (42,9%), hematúria e/ou proteinúria não nefrótica (35,5%), lesão renal aguda (13,2%). Glomerulopatias primárias foram mais frequentes (67,1%), principalmente doença de lesão mínima (DLM) (25,4%), nefropatia por IgA (12,7%), glomerulonefrite mesangioproliferativa (GN) (8,8%). Das glomerulopatias secundárias, nefrite lúpica (NL) foi a mais prevalente (11,8%). No grupo 1, hematúria e/ou a proteinúria não nefrótica foram os principais motivos para BR, ao contrário da SN nos grupos 2 e 3 (p < 0,01). A NL apresentou tendência crescente (período 1-3: 2,6%-5,3%) e a glomeruloesclerose segmentar focal (GESF) apresentou leve tendência decrescente (período 1-3: 3,1%-1,8%), sem significância estatística. Conclusões: A principal indicação para BR foi SN, que aumentou ao longo do tempo, justificando o achado de DLM como principal diagnóstico histológico. A NL apresentou aumento na incidência ao longo do tempo, enquanto os casos de GESF não aumentaram.
RESUMEN
INTRODUCTION: Percutaneous kidney biopsy (KB) is crucial to the diagnosis and management of several renal pathologies. National data on native KB in pediatric patients are scarce. We aimed to review the demographic and clinical characteristics and histopathological patterns in children who underwent native percutaneous KB over 24 years. METHODS: Retrospective observational study of patients undergoing native percutaneous KB in a pediatric nephrology unit between 1998 and 2021, comparing 3 periods: period 1 (1998-2005), period 2 (2006-2013), and period 3 (2014-2021). RESULTS: We found that 228 KB were performed, 78 (34.2%) in period 1, 91 (39.9%) in period 2, and 59 (25.9%) in period 3. The median age at KB was 11 (7-14) years. The main indications for KB were nephrotic syndrome (NS) (42.9%), hematuria and/or non-nephrotic proteinuria (35.5%), and acute kidney injury (13.2%). Primary glomerulopathies were more frequent (67.1%), particularly minimal change disease (MCD) (25.4%), IgA nephropathy (12.7%), and mesangioproliferative glomerulonephritis (GN) (8.8%). Of the secondary glomerulopathies, lupus nephritis (LN) was the most prevalent (11.8%). In group 1, hematuria and/or non-nephrotic proteinuria were the main reasons for KB, as opposed to NS in groups 2 and 3 (p < 0.01). LN showed an increasing trend (period 1-3: 2.6%-5.3%) and focal segmental glomerular sclerosis (FSGS) showed a slight decreasing trend (period 1-3: 3.1%-1.8%), without statistical significance. CONCLUSIONS: The main indication for KB was NS, which increased over time, justifying the finding of MCD as main histological diagnosis. LN showed an increase in incidence over time, while FSGS cases did not increase.
Asunto(s)
Glomerulonefritis por IGA , Glomeruloesclerosis Focal y Segmentaria , Enfermedades Renales , Nefritis Lúpica , Nefrosis Lipoidea , Síndrome Nefrótico , Niño , Humanos , Adolescente , Glomeruloesclerosis Focal y Segmentaria/patología , Hematuria/epidemiología , Hematuria/etiología , Hematuria/patología , Portugal/epidemiología , Riñón/patología , Enfermedades Renales/epidemiología , Enfermedades Renales/patología , Síndrome Nefrótico/diagnóstico , Nefritis Lúpica/patología , Glomerulonefritis por IGA/patología , Proteinuria , Estudios Retrospectivos , BiopsiaRESUMEN
OBJECTIVE: Changes in protein glycosylation are a hallmark of immune-mediated diseases. Glycans are master regulators of the inflammatory response and are important molecules in self-nonself discrimination. This study was undertaken to investigate whether lupus nephritis (LN) exhibits altered cellular glycosylation to identify a unique glycosignature that characterizes LN pathogenesis. METHODS: A comprehensive tissue glycomics characterization was performed in kidney specimens from patients with systemic lupus erythematosus and biopsy-proven LN. A combination of advanced tissue mass spectrometry, in situ glyco-characterization, and ex vivo glycophenotyping was performed to structurally map the repertoire of N-glycans in LN tissue samples. RESULTS: LN exhibited a unique glycan signature characterized by increased abundance and spatial distribution of unusual mannose-enriched glycans that are typically found in lower microorganisms. This glycosignature was specific for LN, as it was not observed in other kidney diseases. Exposure of mannosylated glycans in LN was shown to occur at the cell surface of kidney cells, promoting increased recognition by specific glycan-recognizing receptors expressed by immune cells. This abnormal glycosignature of LN was shown to be due to a deficient complex N-glycosylation pathway and a proficient O-mannosylation pathway. Moreover, mannosylation levels detected in kidney biopsy samples from patients with LN at the time of diagnosis were demonstrated to predict the development of chronic kidney disease (CKD) with 93% specificity. CONCLUSION: Cellular mannosylation is a marker of LN, predicting the development of CKD, and thus representing a potential glycobiomarker to be included in the diagnostic and prognostic algorithm of LN.
Asunto(s)
Riñón/metabolismo , Lupus Eritematoso Sistémico/metabolismo , Nefritis Lúpica/diagnóstico , Polisacáridos/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Progresión de la Enfermedad , Femenino , Glicosilación , Humanos , Nefritis Lúpica/metabolismo , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Abstract The occurrence of ascites after Renal Transplant (RT) is infrequent, and may be a consequence of surgical or medical complications. Case report: 61 year-old, male, history of arterial hypertension, tongue carcinoma and alcoholic habits 12-20g/day. He had chronic kidney disease secondary to autosomal dominant polycystic kidney disease, without hepatic polycystic disease. He underwent cadaver donor RT in September 2017. He had delayed graft function by surgically corrected renal artery stenosis. He was admitted in January 2018 for ascites de novo, with no response to diuretics. HE had visible abdominal collateral circulation. Graft dysfunction, adequate tacrolinemia, Innocent urinary sediment, mild anemia, without thrombocytopenia. Serum albumin 4.0g / dL. Normal hepatic biochemistry. Peritoneal fluid with transudate characteristics and serum albumin gradient > 1.1. Ultrasound showed hepatomegaly, permeable vascular axes, without splenomegaly. Mycophenolate mofetil was suspended, with reduced remaining immunosuppression. He maintained refractory ascites: excluded infectious, metabolic, autoimmune and neoplastic etiologies. No nephrotic proteinuria and no heart failure. MRI: micronodules compatible with bile cysts. Upper Digestive Tract Endoscopy did not show gastroesophageal varicose veins. Normal abdominal lymphoscintigraphy. He underwent exploratory laparoscopy with liver biopsy: incomplete septal cirrhosis of probable vascular etiology some dilated bile ducts. He maintained progressive RT dysfunction and restarted hemodialysis. The proposed direct measurement of portal pressure was delayed by ascites resolution. There was further recovery of the graft function. Discussion: Incomplete septal cirrhosis is an uncommon cause of non-cirrhotic portal hypertension. Its definition is not well known, morphological and pathophysiological. We have not found published cases of post-RT ascites secondary to this pathology, described as possibly associated with drugs, immune alterations, infections, hypercoagulability and genetic predisposition.
Resumo A ocorrência de ascite no pós-Transplante Renal (TR) é infrequente, podendo ser consequência de complicações cirúrgicas ou médicas. Caso clínico: 61 anos, masculino, antecedentes de hipertensão arterial, carcinoma da língua e hábitos alcoólicos 12-20g/dia. Doença renal crônica secundária à doença renal poliquística autossômica dominante, sem poliquistose hepática. Submetido a TR de doador cadáver em setembro de 2017. Atraso na função de enxerto por estenose da artéria renal, corrigida cirurgicamente. Internado em janeiro de 2018 por ascite de novo, sem resposta a diuréticos. Circulação colateral abdominal visível. Disfunção do enxerto, tacrolinemia adequada. Sedimento urinário inocente. Anemia ligeira, sem trombocitopenia. Albumina sérica 4,0g/dL. Bioquímica hepática normal. Líquido peritoneal com características de transudado e gradiente sero-ascítico de albumina > 1,1. Ecografia com hepatomegalia, eixos vasculares permeáveis, sem esplenomegalia. Suspendeu micofenolato mofetil, reduziu restante imunossupressão. Manteve ascite refratária: excluídas etiologias infecciosas, metabólicas, autoimunes e neoplásicas. Sem proteinúria nefrótica e sem insuficiência cardíaca. RM: micronódulos compatíveis com quistos biliares. EDA sem varizes gastroesofágicas. Linfocintigrafia abdominal normal. Submetido a laparoscopia exploradora com biópsia hepática: cirrose septal incompleta de provável etiologia vascular, alguns ductos biliares dilatados. Manteve disfunção progressiva do TR, reiniciou hemodiálise. Proposta medição direta da pressão portal, protelada por resolução da ascite. Recuperação posterior da função de enxerto. Discussão: A cirrose septal incompleta é uma causa incomum de hipertensão portal não cirrótica. A sua definição é morfológica e a fisiopatologia, pouco conhecida. Não encontramos publicados casos de ascite pós-TR secundária a esta patologia, descrita como possivelmente associada a fármacos, alterações imunitárias, infecções, hipercoagulabilidade e predisposição genética.
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Ascitis/etiología , Trasplante de Riñón/efectos adversos , Insuficiencia Renal Crónica/cirugía , Cirrosis Hepática/patología , Ascitis/diagnóstico , Diálisis Renal/normas , Riñón Poliquístico Autosómico Dominante/complicaciones , Funcionamiento Retardado del Injerto/complicaciones , Hipertensión Portal/etiología , Cirrosis Hepática/complicacionesRESUMEN
The occurrence of ascites after Renal Transplant (RT) is infrequent, and may be a consequence of surgical or medical complications. Case report: 61 year-old, male, history of arterial hypertension, tongue carcinoma and alcoholic habits 12-20g/day. He had chronic kidney disease secondary to autosomal dominant polycystic kidney disease, without hepatic polycystic disease. He underwent cadaver donor RT in September 2017. He had delayed graft function by surgically corrected renal artery stenosis. He was admitted in January 2018 for ascites de novo, with no response to diuretics. HE had visible abdominal collateral circulation. Graft dysfunction, adequate tacrolinemia, Innocent urinary sediment, mild anemia, without thrombocytopenia. Serum albumin 4.0g / dL. Normal hepatic biochemistry. Peritoneal fluid with transudate characteristics and serum albumin gradient > 1.1. Ultrasound showed hepatomegaly, permeable vascular axes, without splenomegaly. Mycophenolate mofetil was suspended, with reduced remaining immunosuppression. He maintained refractory ascites: excluded infectious, metabolic, autoimmune and neoplastic etiologies. No nephrotic proteinuria and no heart failure. MRI: micronodules compatible with bile cysts. Upper Digestive Tract Endoscopy did not show gastroesophageal varicose veins. Normal abdominal lymphoscintigraphy. He underwent exploratory laparoscopy with liver biopsy: incomplete septal cirrhosis of probable vascular etiology some dilated bile ducts. He maintained progressive RT dysfunction and restarted hemodialysis. The proposed direct measurement of portal pressure was delayed by ascites resolution. There was further recovery of the graft function. Discussion: Incomplete septal cirrhosis is an uncommon cause of non-cirrhotic portal hypertension. Its definition is not well known, morphological and pathophysiological. We have not found published cases of post-RT ascites secondary to this pathology, described as possibly associated with drugs, immune alterations, infections, hypercoagulability and genetic predisposition.
Asunto(s)
Ascitis/etiología , Trasplante de Riñón/efectos adversos , Cirrosis Hepática/patología , Insuficiencia Renal Crónica/cirugía , Ascitis/diagnóstico , Funcionamiento Retardado del Injerto/complicaciones , Humanos , Hipertensión Portal/etiología , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/complicaciones , Diálisis Renal/normasAsunto(s)
Infecciones por Adenoviridae/complicaciones , Trasplante de Riñón/efectos adversos , Nefritis Intersticial/virología , Complicaciones Posoperatorias/virología , Adulto , Humanos , Huésped Inmunocomprometido , Inmunosupresores/uso terapéutico , Riñón , Masculino , Nefritis Intersticial/tratamiento farmacológico , Receptores de TrasplantesRESUMEN
Currently, uveal melanoma is not considered within the Lynch syndrome tumor spectrum. However, there are studies suggesting a contribution of microsatellite instability in sporadic uveal melanoma tumorigenesis. We report a 45-year-old woman who was referred for genetic counseling due to a family history of Lynch syndrome caused by a MLH1 mutation. She originally underwent enucleation of the right eye secondary to a uveal spindle cell melanoma diagnosed at age 25. The tumor recurred 22 years later presenting as an ovarian metastasis and concurrently a microscopic endometrial endometrioid carcinoma, grade 1/3 was diagnosed. Subsequent studies highlighted that the uveal melanoma showed high microsatellite instability and loss of MLH1 and PMS2 protein expression, with no MLH1 promoter methylation or BRAF mutation. Additionally, a GNAQ mutation was found. We conclude that our patient's uveal melanoma is most likely related to MLH1 germline mutation and thus Lynch syndrome related. To the best of our knowledge, this is the first report of uveal melanoma showing MLH1/PMS2 protein loss in the context of Lynch syndrome.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Melanoma/secundario , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Homólogo 1 de la Proteína MutL/genética , Neoplasias Ováricas/secundario , Neoplasias de la Úvea/secundario , Adulto , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Humanos , Melanoma/genética , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/genética , Neoplasias de la Úvea/genéticaRESUMEN
BACKGROUND: Cancer stem cells are tumor cells that present self-renewal, clonal tumor initiation capacity and clonal long-term repopulation potential. We have previously demonstrated that the co-expression of the breast cancer stem cell (BCSC) markers hyaluronan receptor (CD44) and aldehyde dehydrogenase-1 (ALDH1) in ductal carcinomas in situ could be determinant for disease progression. Combining these established BCSC markers with Ki-67 to evaluate quiescence we sought to identify, evaluate the distribution and estimate the mean percentages of CD44(+)ALDH1(+)Ki-67(-) breast cells. MATERIALS AND METHODS: Triple-immunohistochemistry for CD44, ALDH1 and Ki-67 was applied in a series of 16 normal, 54 non-malignant and 155 malignant breast tissues. Clinical relevance was inferred by associations with markers of breast cancer behavior, progression and survival. RESULTS: The mean percentages of cells with this phenotype increased significantly from non-malignant lesions to high-grade ductal carcinomas in situ, decreasing in invasive ductal carcinomas, as also evidenced by an inverse correlation with histological grade and tumor size. The mean percentage of CD44(+)ALDH1(+)Ki-67(-) cells was also significantly higher in women who developed distant metastasis and died due to breast cancer, and a significant association with human epidermal growth factor type 2 (HER2) negativity was observed. CONCLUSION: Our novel findings indicate that CD44(+)ALDH1(+)Ki-67(-) tumor cells may favor distant metastasis and can predict overall survival in patients with ductal carcinomas of the breast. More importantly, quiescence may have a crucial role for tumor progression, treatment resistance and metastatic ability of BCSCs.
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Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/metabolismo , Isoenzimas/metabolismo , Antígeno Ki-67/metabolismo , Retinal-Deshidrogenasa/metabolismo , Adulto , Familia de Aldehído Deshidrogenasa 1 , Mama/metabolismo , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Metástasis de la Neoplasia , Fenotipo , Receptor ErbB-2/metabolismo , Resultado del TratamientoRESUMEN
McArdle disease typically presents in childhood or young adults with myalgia, exercise intolerance, cramps and myoglobinuria. Deficiency of myophosphorylase enzyme results in inability to degrade glycogen stores, causing glycogen accumulation in muscle tissue and energy deficit. Evolution with rhabdomiolysis may occur and can be complicated with acute kidney injury but rarely, in about 11% of cases, is the initial disease manifestation. We report a case of McArdle Disease in a 38-year-old male patient. The disease went unrecognized despite previous symptoms (myalgia, exercise intolerance and single myoglobinuria episode) until an episode of rhabdomyolisis complicated with oliguric acute kidney injury requiring hemodialysis. The kidney biopsy showed evidence of acute tubular necrosis. Despite normalization of renal function, muscle lysis markers remained abnormal. Metabolic myopathy was suspected and a muscle biopsy was performed. It showed subsarcolemic glycogen deposition and absence of myophosphorylase activity. This case-report underlines the importance of considering metabolic myopathy in patients with acute kidney injury and severe rhabdomyolisis.
A doença de McArdle apresenta-se tipicamente por mialgias, intolerância aos esforços, cãibras e mioglobinúria na infância ou jovens adultos. A deficiência hereditária da enzima miofosforílase incapacita a degradação de glicogénio, com consequente acumulação no tecido muscular e défice energético. A rabdomiólise pode ocorrer e complicar-se de lesão renal aguda mas raramente, em cerca de 11% dos casos, é manifestação inicial da doença. Apresentamos um caso de Doença de McArdle num paciente de 38 anos de idade. Tinha antecedentes de mialgias, intolerância aos esforços e episódio isolado de mioglobinúria. A doença foi diagnosticada num episódio de rabdomiólise grave complicada de lesão renal aguda oligúrica, com necessidade de hemodiálise. A biópsia renal demonstrou necrose tubular aguda. Apesar da recuperação renal, os marcadores de lise muscular permaneceram elevados. Na suspeita de miopatia metabólica realizou biópsia muscular que revelou deposição subsarcolémica de glicogénio e ausência de atividade da miofosforilase. As miopatias metabólicas devem ser consideradas na abordagem de LRA associada a rabdomiólise severa.
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Lesión Renal Aguda/etiología , Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Rabdomiólisis/etiología , Adulto , Enfermedad del Almacenamiento de Glucógeno Tipo V/diagnóstico , Humanos , MasculinoRESUMEN
Lymphocytic gastritis (LG) is a chronic inflammatory process of poorly understood pathogenesis. We report the case of a 12-year-old premenstrual girl with refractory iron deficiency anemia in which the oral iron absorption challenge suggested iron malabsorption. Laboratory studies ruled out celiac disease and autoimmune gastritis, and carbon-13 urea breath test for Helicobacter pylori was also negative. Upper endoscopy with gastric body and antral mucosa biopsies revealed a LG with focal intestinal metaplasia and H. pylori infection. H. pylori eradication was undertaken with success and 3 months later her hematologic parameters normalized. Histologic reevaluation showed disappearance of LG. This case shows that investigation of malabsorption disease in the presence of refractory iron deficiency anemia can lead to the diagnosis of important gastric diseases, even in the absence of gastrointestinal symptoms. This nonceliac child was diagnosed with a severe histopathologic pattern of LG, with potential risk of malignant transformation, which was completely reverted with adequate H. pylori eradication treatment.
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Anemia Ferropénica/microbiología , Gastritis/sangre , Gastritis/microbiología , Infecciones por Helicobacter/sangre , Helicobacter pylori/aislamiento & purificación , Anemia Ferropénica/patología , Niño , Femenino , Gastritis/patología , Infecciones por Helicobacter/patología , Humanos , Linfocitosis/sangre , Linfocitosis/microbiología , Linfocitosis/patologíaRESUMEN
Whipple's disease (WD) is a chronic infection caused by Thropheryma whipplei that usually manifests with intestinal, articular, pulmonary, neurological and cardiac abnormalities. Rarely, WD has been associated with renal AA amyloidosis.We report a 50 year-old male with nephrotic syndrome and renal failure whose renal biopsy revealed extensive AA amyloidosis. Amyloid was not found in other organs, namely in gastrointestinal tract and bone marrow. There was no evidence of chronic inflammatory disease, and despite detailed investigation, the diagnosis of the underlying disease remained obscure. Eight months after referral he started peritoneal dialysis. Three years later he developed anorexia, weight loss, anemia, and recurrent attacks of non-bloody diarrhea. A biopsy of the small intestine showed typical histological findings of WD and PCR was positive for T. whipplei. He was treated with ceftriaxone followed by co-trimoxazole, with remission of complaints and histological features. Three years later the patient underwent successful cadaveric kidney transplantation. In this case, AA amyloidosis preceded the manifestations of WD. To the best of our knowledge, this is the first report of kidney transplantation in a patient with amyloidosis due to WD. Recurrence of amyloidosis in renal graft is not expected.